A Multicenter Randomized Controlled Clinical Trial Evaluating Two Application
Regimens of Dehydrated Human Amniotic Membrane and Standard of Care vs
Standard of Care Alone in the Treatment of Venous Leg Ulcers

IntroductionVenous leg ulcerations(VLUs) frequently represent a significant clinical challenge. Dehydrated human amnion and chorion allografts have shown great promise in the treatment of recalcitrant VLUs when compared to standard wound care(SOC) alone. Adding placental grafts into the treatment regimen is often successful as they are rich in extra cellular matrix proteins, growth factors, and cytokines, and as such can induce angiogenesis and dermal fibroblast proliferation which can lead to accelerated healing.MethodsThe goal of this study was to compare aseptically processed dehydrated human amnion and chorion allograft(dHACA) applied weekly or biweekly combined with standard of care versus standard of care alone in facilitating wound closure in non-healing VLUs. The research was reviewed and approved by the Western Institutional Review Board and registered on ClinicalTrials.gov and conducted at 8 wound care centers. Patients with non healing VLUs treated with SOC(appropriate debridement, primary absorptive dressing and multilayercompression) after a 2-week screening period were randomized to either receive SOC (20 patients) or wound size-specific dHACA plus SOC applied weekly(20 patients) or wound-size-specific dHACA plus SOC applied biweekly(20 patients) for up to 12 weeks. Primary endpoint of this clinical trial was percent of patients healed(completely epithelialized )at 12 weeks. Secondary endpoints included the proportion of ulcers achieving 40% closure at 4 weeks and the incidence of adverse events(AEs).ResultsAmong 101 patients screened for eligibility, 60 were eligible and enrolled. At 12 weeks, significantly more VLUs healed in the two dHACA-treated groups(30/40,75%)than in the SOC group(6/20, 30%),p = 0.001. Treatment with dHACA remained significant after adjustment for wound area(p = 0.002),with an odds ratio of 8.7(95% confidence interval(2.2-33.6).Only six VLUs(30%) healed in the SOC group compared to 15 75%) in the weekly dHACA group(p = 0.02)and 15(75%) in the biweekly dHACAgroup(p =0.02).There were no significant differences in the proportion of wounds withpercent area reduction(PAR )≥40% at 4 weeks among all groups. The AE rate was63.5%. Among the 38 AEs, none were graft- or procedure-related, Conclusion Aseptically processed dHACA should be considered as a viable option for the refractory venous leg wounds whether applied weekly or bi-weekly